Small-molecule CD73 inhibitors for the immunotherapy of cancer: a patent and literature review (2017-present).

Considerable advances have been reported in the design of nucleotide/nucleoside-based CD73 inhibitors, after the X-ray crystal structure of the enzyme in complex with the non-hydrolyzable ADP analog, adenosine (α,β)-methylene diphosphate (AMPCP), was reported. A large number of highly effective such inhibitors are now available, through modifications of the nucleobase, sugar and zinc-binding groups of the lead. Few classes of non-nucleotide inhibitors were also reported, including flavones, anthraquinone ssulfonates, and primary sulfonamides. A highly potent ssmall-molecule CD73 inhibitor, AB680, is presently in the early phase of clinical trials as immunotherapeutic agents against various types of cancer.